tbuckley/cabot-search huggingface dataset:
Phase II evaluation of combination immunotherapy with CV301, N-803, bintrafusp alfa, and M9241 in patients with advanced small bowel and colorectal cancers.
Authors: Danielle M. Pastor, Jason M. Redman, Charalampos S. Floudas, Elizabeth Lamping, Deneise C. Francis, Lisa M. Cordes, Jennifer L. Marte, Jeffrey Schlom, James L. Gulley, Julius Strauss
Journal: Journal of Clinical Oncology (2023)

116 Background: Although immune checkpoint inhibitors (CPI) are inactive as monotherapy for microsatellite stable (MSS) mCRC, preclinical modeling suggests that addition of other immune-oncology agents can produce antitumor activity. CV301 is a poxviral vaccine against CEA and MUC1. N-803 is an IL-15 superagonist. M9241 is tumor-targeted IL-12. Bintrafusp alfa (BA) is a bifunctional anti-PD-L1/TGF-βRII fusion protein. Methods: Patients with advanced MSS or proficient mismatch repair (pMMR) small bowel or CRC were eligible (NCT04491955). Patients enrolling to Arm 1 received triple therapy with BA 1200 mg IV every 2 weeks, N-803 15 mcg/kg SC every 4 weeks, and CV301 SC on D1, D15, D29, and monthly, thereafter. Patients enrolling to Arm 2 received quadruple therapy, with M9241 (8 mcg/kg or 16.8 mcg/kg SC every 4 weeks) plus BA (300 mg or 1200 mg IV), N-803 (10 mcg/kg SC) and CV301 SC, depending on dose escalation schedule. Results: Thirty patients (2 small intestinal, 17 colon, 11 rectal) were treated. All patients had received prior 5-fluorouracil-based treatment, with 29/30 (96.7%) having received ≥ 2 lines of systemic therapy. Twelve patients received triple therapy; 18 received quadruple therapy. Grade 3 treatment-related AEs (TRAEs) occurred in 8 patients (26.7%); anemia occurred most commonly (n = 5), with grade 3 gastrointestinal hemorrhages occurring in 2 patients (on quadruple therapy). Other grade 3 TRAEs included elevated cardiac troponin, AST, and alkaline phosphatase (n = 1 each; all with triple therapy), and adrenal insufficiency (n = 1; quadruple therapy). No grade 4 or 5 TRAEs occurred. Triple therapy resulted in disease reduction in 2 patients (7.5%, 25.6%); quadruple therapy resulted in disease reduction in 2 patients (26.7%, 70.6%). Median overall survival (OS) for triple and quadruple therapy have not been reached, with 12 month survival being 66.7% (95% CI: 33.7-86.0%) for triple therapy and 77.2% (95% CI: 43.3-92.3%) for quadruple therapy. Conclusions: Combination therapies with CV301, N-803, bintrafusp alfa, and M9241 had manageable safety profiles. Preliminary clinical activity was observed in patients with advanced MSS/pMMR small bowel or CRC. Median OS was promising as compared to historical median survivals of 6-7 months following receipt of multiple lines of therapy. Clinical trial information: NCT04491955 .
Phase II trial of rosuvastatin combined with chemoradiation therapy (CRT) in the treatment of high-risk locally advanced rectal cancer (STARC trial).
Authors: Jose Gerard Monzon, Kurian Joseph, Eric Xueyu Chen, Patricia A. Tang, Rishi Sinha, Kristopher Dennis, Rachel Anne Goodwin, Diane Severin, Jim Dimitroulakos, Michael M. Vickers
Journal: Journal of Clinical Oncology (2023)

131 Background: Pre-clinical evidence suggest that statins have antiproliferative, proapoptotic, and anti-invasive properties. Also, statins can sensitize cancer tissues and protect normal tissues to the effects of radiation. A standard treatment of locally advanced rectal cancer (LARC) involves neoadjuvant CRT followed by surgery and adjuvant chemotherapy. Retrospective analyses of statin use in rectal cancer patients receiving CRT suggest a higher pathological complete response rate (pCRr). Methods: Patients with clinical stage II-III rectal adenocarcinoma, within 5 cm of the anal verge (AV) or less than 12cm from the AV with threatened circumferential resection margin were treated with rosuvastatin 40 mg daily starting 2 weeks prior to the start and until 4 weeks after the end of CRT. The primary objective of the study was pCRr. Secondary objectives included, near-CRr, Ro resection rate (RR), sphincter preservation, 3-year relapse free survival (RFS), 3-year overall survival (OS), toxicity and safety. A Simon’s minimax two-stage design was used to determine significance. A pCRr of ≥25% was required to reject the null hypothesis. RFS and OS rates were calculated using the Kaplan-Meier product-limit method. Results: Forty-five patients were enrolled from 2016 to 2021. Sixty-seven percent were male with a median age of 54 (IQR 37- 61), 97.8% (44/45) had ECOG PS of 0-1, 15.6% (7/45) were cT4, 73.3% (33/45) were cN+. Of the 38 evaluable patients, 9 had a pCR (23.7%), an additional 9 had a near-pCR (23.7%). With a median follow-up of 3.26 years, the 3-year OS rate was 96.3% (95% CI (0.765, 0.995)) and the 3-year DFS rate was 77.9% (95% CI (0.604, 0.883)) in the evaluable patients. One patient elected for non-operative management and has an on-going clinical CR for the last 15 months. Surgery was sphincter sparing in 17 patients (43.6%) and an 87.2% Ro RR was observed. Toxicities attributable to rosuvastatin included: two patients with elevations in liver enzymes, grade 3. Remaining toxicities were grade 2 or less, with the most common toxicities being fatigue (n = 5) and pain (n = 3). Only 2 patients experienced CPK elevations, both grade 2. Conclusions: The addition of rosuvastatin to nCRT resulted in a considerable complete and near-complete response rate with an acceptable toxicity profile. Rosuvastatin treatment should be studied further in the total neoadjuvant and non-operative management settings for locally advanced rectal cancer. Clinical trial information: NCT02569645 .
Costs of adverse event management associated with first-line cetuximab or panitumumab in patients with metastatic colorectal cancer in Spain.
Authors: Begoña Graña Suárez, Noelia Tarazona, Olga Duran Moran, Ana Fernandez Gonzalez, Heidi De los Santos Real, Chris P. Pescott
Journal: Journal of Clinical Oncology (2023)

83 Background: Patients with RAS wild-type metastatic colorectal cancer (mCRC) in Spain may be treated with an epidermal growth factor receptor inhibitor: cetuximab (cet) or panitumumab (pan), in combination with chemotherapy (CT). Several factors may influence the choice of treatment regimen, including adverse event (AE) management, as cet- and pan-based therapies have distinct individual safety profiles. Patients may experience multiple adverse events during treatment. This study aimed to estimate the associated financial impact on Spain’s National Health System (SNHS). Methods: An economic model was developed to project the mean number of AEs per patient (p-p) and to estimate p-p and population-level costs of AE management (cAEm) associated with first-line cet+CT and pan+CT treatment regimens. Data on common and very common AEs and their severity were sourced from the summaries of product characteristics and a meta-analysis by Petrelli, et al. Categorical values were converted into numerical values using the mean values of the frequencies for each AE. Applicable resource costs were obtained from a Spanish database with health unit costs from official records, and from literature on oncology treatment-related costs. The eligible patient population was determined from published and grey literature, and market research. AEs of grade 1-2 were assumed to be treated in an outpatient setting, and those of grade 3-4 treated in an inpatient setting. The model inputs were validated by clinical oncologists in Spain. Results: An estimated 3,794 (cet+CT) and 2,325 (pan+CT) eligible patients received first-line treatment for mCRC. For patients receiving cet+CT or pan+CT, the average frequency of AEs p-p was estimated to be 7.2 (cet+CT) and 17.2 (pan+CT), with estimated p-p cAEms of €5,655 and €13,571, respectively. Conclusions: The lower rates of AEs for cet+CT may result in a reduced AE burden for eligible patients with mCRC, with estimated savings of €7,917 p-p on average. Although overall costs and clinical outcomes should be considered, treatment with cet+CT could yield annual cAEm savings for the SNHS of 35%. Future studies should consider the impact of AE management in a real-world setting.
Camrelizumab plus low-dose apatinib and SOX in the first-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: A single-arm, dose escalation and expansion study (SPACE study).
Authors: Xiaofeng Chen, Hao Xu, Deqiang Wang, Xiaobing Chen, Kangxin Wang, Guangfu Jin, Yongbin Ding, Jie Tang, Yueyu Fang, Hui Sun, Qiusheng Jiang, Lanlan Pan, Yitong Tian, Rong Wang, Tongpeng Xu, Lijuan Meng, Fengyuan Li, Yongqian Shu, Fen Guo
Journal: Journal of Clinical Oncology (2023)

365 Background: The dose escalation phase was presented early, and confirmed that the recommended phase II dose (RP2D) was camrelizumab (200 mg, d1) plus apatinib (250 mg, qd), S-1(40 mg, bid, d1-14) and oxaliplatin (130 mg/m 2 , d1) every 3 weeks followed by camrelizumab (200 mg, d1) plus apatinib (250 mg, qd) every 3 weeks. Methods: Patients (pts) aged 18-75 years, with unresectable or potentially resectable G/GEJ adenocarcinoma, HER2-negative or unknown HER2 status and no previous systemic therapy, were enrolled to receive combination therapy. Primary endpoint was Objective response rate (ORR) by RECIST 1.1, secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR), surgical resection rate and safety. Results: From Jun, 2020 to July 2022, 35 pts were enrolled (9 pts in dose escalation phase, 26 pts in dose expansion phase), with a median follow-up of 8.0 months (95% CL, 6.7-12.2). Median age (range) was 59(19-68), 94.3% (33/35) were male, 20% (7/35) were diagnosed with GEJ adenocarcinoma, 60% (21/35) had liver metastases. At data cutoff, 33 pts were included in the efficacy analysis. The ORR was 90.9%, with 30 (90.9%) PR. SD were 1 (3.0%) with a DCR of 93.9%. In addition, 9 pts showed an unconfirmed PR with a confirmed ORR of 80.8%. Median PFS was 10.2 months (95% CI, 5.5-22.3), with the median OS not reached yet. Conversion to resectable G/GEJ adenocarcinoma was identified in 9 (25.7%) pts. Of them, 2 pts were observed complete pathology response. 94.3% pts experienced treatment related adverse event (TRAE), with 45.7% being grade ≥3. The most frequent grade ≥3 TRAE were GGT increased (31.4%, 11/35), rash (11.4%, 4/35), alkaline phosphatase increased (11.4%, 4/35)、neutrophil count decreased (8.6%, 3/35). No new safety signal was identified. Conclusions: Camrelizumab plus apatinib and SOX followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as first line therapy for patients with G/GEJ adenocarcinoma. Clinical trial information: ChiCTR2000034109 .
Phase I study of proton therapy in adjuvant pancreatic cancer (PROTON-PANC).
Authors: Benjamin Adam Weinberg, Hongkun Wang, Marcus Smith Noel, Aiwu Ruth He, John Marshall, Louis M. Weiner, Thomas M. Fishbein, Emily R. Winslow, Patrick G. Jackson, Juan F. Guerra, Francisco Aguila, Keith Robert Unger
Journal: Journal of Clinical Oncology (2023)

709 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 10%. The current standard of care for patients with resectable disease is surgical resection followed by 6 months of adjuvant mFOLFIRINOX (mFFX) chemotherapy. As survival outcomes and distant recurrence rates improve with the use of mFFX, locoregional recurrence remains a significant cause of morbidity and mortality. We sought to integrate short-course proton radiation therapy (PRT) to the operative bed between cycles of adjuvant chemotherapy in patients with resected PDAC of the pancreatic head. Methods: Between 2019 and 2022, patients with resected PDAC with an R0 or R1 resection on adjuvant mFFX were enrolled in a phase I trial using a 3+3 dose-escalation schema (NCT03885284). Patients received mFFX as used in the PRODIGE 24 study and also received short-course PRT delivered over 1 week in 5 fractions (5 GyE each) between cycles 6 and 7 of mFFX. In dose level 1 (DL1), patients received PRT on days 15-19 in a 28-day cycle before starting cycle 7, and in dose level 2 (DL2) patients received PRT on days 8-12 in a 21-day cycle before starting cycle 7. Results: Nine patients were enrolled on the trial, median age 66 (range 52-78). Five had R0 resections, 4 had R1 resections, and 5 had node-positive disease. No patients received preoperative therapy, and none underwent vein reconstruction. Three patients were enrolled on DL1 and 6 patients on DL2. One dose limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed the planned 12 cycles of mFFX (range 7-12, median 11). None of the patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence free. With a median follow up from date of chemotherapy start of 12.5 months, median time to disease recurrence was 12 months (95% confidence interval [CI] 4-not reached [NR]), and median overall survival has not been reached (95% CI 6-NR, 2-year survival rate 57%). Conclusions: PRT integrated within adjuvant mFFX was well-tolerated and no local recurrence was observed for patients with resected PDAC. These findings warrant being confirmed in a phase II trial. Clinical trial information: NCT03885284 .
BREAKWATER safety lead-in (SLI): Encorafenib (E) + cetuximab (C) + chemotherapy for <i>BRAF</i><sup>V600E</sup> metastatic colorectal cancer (mCRC).
Authors: Scott Kopetz, Takayuki Yoshino, Tae Won Kim, Rona Yaeger, Jayesh Desai, Harpreet Singh Wasan, Eric Van Cutsem, Fortunato Ciardiello, Tim Maughan, Cathy Eng, Jeanne Tie, Elena Elez, Sara Lonardi, Xiaosong Zhang, Chin-Hee Chung, Tiziana Usari, Tim Nicholz, Danielle A. Murphy, Josep Tabernero
Journal: Journal of Clinical Oncology (2023)

119 Background: Based on the phase 3 BEACON study (NCT02928224), BRAF inhibitor (i) encorafenib (E) + EGFRi cetuximab (C) was approved for the treatment (tx) of previously treated patients (pts) with BRAF V600E mCRC, with mPFS of 4.3 months (mo) and ORR of 19.5%. In the phase 2 ANCHOR study (NCT03693170), mPFS was 5.8 mo and ORR was 48% for 1L EC + binimetinib in BRAF V600E mCRC. To further assess 1L approaches, the ongoing phase 3 BREAKWATER study (NCT04607421) is evaluating EC ± chemotherapy vs standard-of-care chemotherapy in BRAF V600E mCRC. Here, we present updated safety and antitumor activity data as well as biomarker data from the BREAKWATER SLI. Methods: Inclusion criteria for the SLI were BRAF V600E mCRC (blood or tumor tissue), ≤1 prior systemic tx for mCRC, and ECOG PS 0/1. Pts previously treated with BRAFi/EGFRi or both oxaliplatin and irinotecan were excluded. Pts received E 300 mg daily + C 500 mg/m 2 every 2 weeks (Q2W) + either mFOLFOX6 Q2W (n=27) or FOLFIRI Q2W (n=30) in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was frequency of dose-limiting toxicities. Secondary endpoints included safety, pharmacokinetics, and antitumor activity. Exploratory endpoints included evaluation of plasma (circulating tumor DNA [ctDNA] genomic profiling) and tumor tissue (molecular profiling) biomarkers. Updated results from the BREAKWATER SLI will be presented, including overall safety and tolerability and antitumor activity. Biomarker data, including changes from baseline in BRAF V600E ctDNA following treatment (Cycle 1 Day 15, Cycle 2 Day 15 and Cycle 7 Day 1) and MSI status of pts, will also be presented. Expected conclusions will be included in the final abstract. Clinical trial information: NCT04607421 .
Second-line bevacizumab plus FOLFOX in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-based chemotherapy.
Authors: Sang Hoon Chun, Jung Hoon Kim, Seung-Jin Kwag, Myoung Hee Kang, Ji-Ho Park, Gyeong-Won Lee, Jung Hun Kang
Journal: Journal of Clinical Oncology (2023)

157 Background: There is a rarity of evidence for retreatment with oxaliplatin for metastatic colorectal cancer (mCRC), especially in combination with bevacizumab. This is a retrospective study of second line bevacizumab (Bev) plus FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-containing chemotherapy. Methods: Patients with age older than 18 and histologically confirmed metastatic colorectal cancer treated with second line bevacizumab plus FOLFOX in a single institute between 2015 and 2020 were enrolled. History of previous adjuvant chemotherapy regimens in patients with metachronous metastatic colorectal cancer was analyzed. Progression-free survival (PFS) and overall survival (OS) of the second line treatment were calculated using Kaplan-Meier method and compared between patients pretreated with adjuvant oxaliplatin (ReOx) and oxaliplatin-naive patients (control) with the log rank test. Results: A total of 72 patients were included. 23 patients (ReOx) were pretreated with adjuvant oxaliplatin and 49 patients (control) were oxaliplatin-naive before the second line treatment. There was a tendency of younger age in the ReOx group, but not statistically significant. Liver metastasis was significantly more frequent in the control group. The median PFS and OS in the ReOx group and the control group were 4.3 months (95% confidence interval [CI], 3.67–21.50) versus 5.5 months (95% CI, 4.23–8.20, hazard ratio [HR] = 0.84), and 10.5 months (95% CI, 5.40–30.37) versus 9.4 months (95% CI, 6.00–14.9, HR = 1.01) respectively. There was no significant difference of PFS ( p= 0.523) and OS ( p= 0.9745) between two groups. Conclusions: This study suggests a potential survival benefit of bevacizumab plus FOLFOX for mCRC patients previously treated with adjuvant oxaliplatin-containing treatment comparable to oxaliplatin-naive patients. [Table: see text]
Symptom burden over time among early-onset young adult colorectal cancer survivors.
Authors: Justin Cheng, Bahram Nadim, Julia Stal, Sally Cohen-Cutler, Phuong Gallagher, Jonathan N Kaslander, Priscilla Marin, Afsaneh Barzi, Heinz-Josef Lenz, David R. Freyer, Kimberly Ann Miller
Journal: Journal of Clinical Oncology (2023)

88 Background: From 1995-2016, rates of colorectal cancer (CRC) have increased among young adults (YA) under 50 years by 2% annually, despite overall rates of CRC among adults over age 65 decreasing. Unfortunately, this population is disproportionately affected by diagnosis at later stage of disease due to systematic and healthcare factors. Such late diagnoses are associated with higher symptom burden among survivors; however, symptom burden among YA early-onset CRC (EOCRC) survivors is poorly understood. The present study aims to characterize symptom burden among YA EOCRC survivors. Methods: A cross sectional survey was administered online in collaboration with a national organization for YA CRC survivors. Respondents (18-49 years) were EOCRC survivors who were 6-36 months from diagnosis/relapse. Survivors endorsed symptoms they experienced among 23 common CRC late effects. Responses were stratified by symptom duration (6-18 versus 19-36 months) to examine differences in endorsement rates among respondents. Results: Respondents (n=235) were colon (n=86) and rectal (n=149) cancer survivors, primarily male 63%, diagnosed at 32.4 years (SD=6.65), with an average of 5.1 (SD=2.57) symptoms. Overall, the most highly reported symptoms were fatigue, perceived change in appearance after treatment, and nail color changes. Comparisons of 6-18 and 19-36 months-from-diagnosis groups revealed similar symptom endorsement rates, with those 19-36 months from diagnosis endorsing constipation/diarrhea, anal bleeding, and incisional discomfort at higher rates than those 6-18 months from diagnosis. The 6-18 and 19-36 months-from-diagnosis groups carried similar symptom burdens of 4.9 (SD=2.57) and 5.1 (SD=2.58), respectively. Conclusions: YA EOCRC survivors endorse numerous symptoms that may interfere with their daily living and quality of life. Similarities in endorsement between 6-18 month and 19-36-month groups suggest symptoms may become chronic and persist beyond cancer treatment. Fortunately, many symptoms can be mitigated or prevented with proper medical and/or psychosocial intervention, patient education, and resource availability. Providers can leverage these findings in their evaluation of YA EOCRC patients during treatment and follow-up care to ensure the delivery of optimal symptom management. [Table: see text]
Advantages of minimally invasive surgery for remnant gastric cancer: A multi-institutional cohort study.
Authors: Ryuhei Aoyama, Shigeru Tsunoda, Ryosuke Okamura, Yoshito Yamashita, Hiroaki Hata, Yousuke Kinjo, Akira Miki, Seiichiro Kanaya, Michihiro Yamamoto, Koichi Matsuo, Dai Manaka, Atsushi Itami, Takatsugu Kan, Tetsuo Ito, Kenjiro Hirai, Hisahiro Hosogi, Tatsuto Nishigori, Shigeo Hisamori, Nobuaki Hoshino, Kazutaka Obama
Journal: Journal of Clinical Oncology (2023)

357 Background: Remnant gastric cancer (RGC) is defined as a cancer arising in the remnant stomach after initial gastrectomy, regardless of the previous disease or surgical procedure. Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for RGC remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. Methods: We collected the data of patients with RGC who underwent surgery with curative intent between 2005 and 2020 from 17 institutions in Japan, and performed a propensity score (PS) matching analysis to compare the short- and long-term outcomes of MIS with open surgery. Results: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 (95% confidence interval [CI]: 0.45–1.27) and 0.65 (95% CI: 0.32–1.29), respectively. The MIS group had significantly less blood loss (50 ml vs. 361 ml, P&lt;0.001) and a shorter hospital stay (13 days vs. 16 days, P=0.009) than the open surgery group, while the operative time was longer in the MIS group (344 min vs. 273 min, P&lt;0.001). The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival rates were 77.9% in the MIS group and 76.2% in the open surgery group (hazard ratio [HR], 0.78; 95% CI: 0.45–1.36). The 3-year relapse-free survival rates were 71.9% in the MIS group and 62.2% in the open surgery group (HR, 0.71; 95% CI: 0.44–1.16). Locoregional recurrence occurred in three patients (3.2%) in the MIS group and four patients (4.3%) in the open surgery group. There were also no differences in the other patterns of recurrence between the groups. Conclusions: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.